Trial reportThe Journal of clinical investigation2020
TGF-β-induced epigenetic deregulation of SOCS3 facilitates STAT3 signaling to promote fibrosis.
Trial report in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
88 citing papers in PubMed, 125 citations in OpenAlex.
- Bufalin post-transcriptionally suppresses STAT3 to alleviate renal ferroptosis and tubulointerstitial fibrosis in diabetic kidney disease.Renal failure · 2026Article
- TGF-β1 Induced Methylation to Regulate SOCS3 Expression in Abnormal Activation of Vocal Fold Fibroblasts.World journal of otorhinolaryngology - head and neck surgery · 2026Article
- Circadian dysregulation of leptin and its role in skin inflammation and obesity: an integrative perspective.Endocrine · 2026Review
- RaFiST: a radiomics model for non-invasive stratification of tumor fibrosis and prognostic prediction in non-small cell lung cancer.European radiology · 2026Article
- Targeting canonical TGFβ/SMAD3 and ERK1/2 signaling in human valve interstitial cells to modulate immune-fibrotic responses in rheumatic heart disease.Journal of physiology and biochemistry · 2026Article
- Formononetin alleviates ovarian fibrosis and inflammation via targeting SOCS3 and inhibiting TGF-Chinese herbal medicines · 2026Article
- Epigenetic orchestration of scar formation: Therapeutic potential of targeting DNA methylation and non‑coding RNAs in cutaneous fibrosis (Review).Molecular medicine reports · 2026Review
- The Tumor-Promoting Role of ADM in Bladder Cancer and its Mediated Mechanisms of Cell Death via PKR and STAT1.Applied biochemistry and biotechnology · 2026Article
- Equine mesenchymal stromal cells dual-primed with TGF-β1 and IL-1β or TNF-α improve epithelial healing.Research square · 2026Article
- Deep phenotyping of skin tissue remodeling in patients with systemic sclerosis treated with CD19-CAR T cells.Nature communications · 2026Article
- Induction of fibrosis in human kidney organoids delineates mechanisms and therapeutic targets of fibrotic kidney disease.Stem cell research & therapy · 2026Article
- Mechanisms of fibrotic tissue remodelling: insights from systemic sclerosis.Nature reviews. Rheumatology · 2026Review
- Smarce1-dependent modulation of Stat3 signaling governs cardiomyocyte proliferation.Biological research · 2026Article
- Plant-Derived Agents and Systemic Sclerosis: A Systematic Review of Therapeutic Potential and Molecular Mechanisms.Current issues in molecular biology · 2026Review
- Current insights into PHF14: molecular features and functional roles.Frontiers in molecular biosciences · 2026Review
- An intricate relationship between fibrosis and autoimmune diseases: a specific focus on unraveling its molecular, immunological, and epigenetic drivers.Frontiers in immunology · 2026Review
- Signaling pathway networks in frozen shoulder fibrosis: from inflammatory initiation to fibrotic progression.Frontiers in medicine · 2026Review
- Tissue-Resident Memory T Cells in Rheumatoid Immune Diseases: Pathogenic Mechanisms and Therapeutic Strategies.Biomedicines · 2025Review
- Epigenetic regulatory mechanisms of autoimmune skin diseases: novel biomarkers and therapeutic prospects.Clinical epigenetics · 2025Review
- IL27RA promotes the proliferation and metastasis of hepatocellular carcinoma cells by regulating TGFβR1.Scientific reports · 2025Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fibroblasts are key effector cells in tissue remodeling. They remain persistently activated in fibrotic diseases, resulting in progressive deposition of extracellular matrix. Although fibroblast activation may be initiated by external factors, prolonged activation can induce an "autonomous," self-maintaining profibrotic phenotype in fibroblasts. Accumulating evidence suggests that epigenetic alterations play a central role in establishing this persistently activated pathologic phenotype of fibroblasts. We demonstrated that in fibrotic skin of patients with systemic sclerosis (SSc), a prototypical idiopathic fibrotic disease, TGF-β induced the expression of DNA methyltransferase 3A (DNMT3A) and DNMT1 in fibroblasts in a SMAD-dependent manner to silence the expression of suppressor of cytokine signaling 3 (SOCS3) by promoter hypermethylation. Downregulation of SOCS3 facilitated activation of STAT3 to promote fibroblast-to-myofibroblast transition, collagen release, and fibrosis in vitro and in vivo. Reestablishment of the epigenetic control of STAT3 signaling by genetic or pharmacological inactivation of DNMT3A reversed the activated phenotype of SSc fibroblasts in tissue culture, inhibited TGF-β-dependent fibroblast activation, and ameliorated experimental fibrosis in murine models. These findings identify a pathway of epigenetic imprinting of fibroblasts in fibrotic disease with translational implications for the development of targeted therapies in fibrotic diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.